This is the blog for Yale's undergrad course ANTH204:
An introduction to the patterns and processes of human genetic variation. Topics include: human origins and migration; molecular adaptations to environment, lifestyle and disease; ancient and forensic DNA analyses; and genealogical reconstructions.

Wednesday, October 19, 2011

Turning On Fetal Hemoglobin: The Key to Reversing Sickle Cell Anemia?

Background

Anemia, joint pain, swollen spleen and frequent severe infections are all common symptoms of Sickle Cell Disease (SCD), a group of inherited red blood cell disorders that result from the presence of a mutated form of hemoglobin, hemoglobin S (HbS).First described by Herrick in 1910, SCD is an autosomal recessive disorder that causes from a single code letter change in the DNA, or point mutation. In turn, this change alters one of the amino acids in the hemoglobin protein: Valine sits where glutamic aid should be. Valine makes the hemoglobin molecules stick together, forming long fibers that distort the shape of the red blood cells that resemble sickles. Sickle cells die early, which results in a constant shortage of red blood cells. Additionally, elongated blood cells get stuck in small blood vessels and clog the blood flow. SCD causes significant mortality and morbidity, particularly in people of Mediterranean and African ancestry.

Hypothesis

“For three decades biomedical researchers have hypothesized that fetal hemoglobin could be turned off if the mechanism of hemoglobin switching could be understood.”

New Finding

On October 13, 2011 the Howard Huges Medical Institute (HHMI) published an article that explains how turning on fetal hemoglobin can reverse sickle cell anemia (SCA).An HHMI study led by Dr. Stuart Orkin of Children’s Hospital Boston, Dana Farber Cancer Institute and Harvard Medical School has shown that silencing a protein known as BCL11A can reactivate fetal hemoglobin production in adult mice. In fact, their research demonstrates that BCL11A is one of the primary factors involved in turning off hemoglobin production.In regard to methods of the study Dr. Orkin’s and his team used a genetic manipulation of a mouse model of SCD. A detailed review of the findings, that should further reveal methods used, will be published by Dr. Orkin and his team.

Implications

BLC11A could serve as a target for treating SCD and related blood disorders. Of his research Dr. Orkin says: “I think we’ve demonstrated that a single protein in the cells is a target that, if interfered with, would provide enough fetal hemoglobin to make patients better.” However, further research is needed into the working of BCL11A, to determine a model of transference from a mouse model of SCD to a human one.